No indications for altered EEG oscillatory activity in patients with chronic post-burn itch compared to healthy controls

A large proportion of patients with burn injuries develop chronic itch, which impacts quality of life. The underlying pathophysiological mechanisms are poorly understood. This cross-sectional pilot study investigates whether altered cortical oscillatory processes are involved in chronic post-burn itch. Continuous electroencephalography (EEG) data were recorded during rest and stimulation of non-injured skin, inducing itch (histamine and electrical) and cold-pressor task pain for 15 adults with chronic post-burn itch and 15 matched healthy controls. Quantitative metrics comprised oscillatory power and peak frequencies in theta, alpha, and beta bands. No statistical differences between patients and healthy controls were found in oscillatory activity during rest or stimulation, with Bayesian analysis suggesting equivocal evidence. However, post-traumatic stress symptoms and duration of chronic itch may be associated with changes in oscillatory activity. A lack of differences in cortical oscillatory processing and itch levels at non-injured sites, suggests that itch symptoms have a localised character in this sample of patients with post-burn itch. For future studies, a biopsychological approach with integration of peripheral and central nervous system techniques, linear and non-linear EEG analysis, injured and non-injured stimulation sites, and incorporation of individual characteristics is recommended. Insight into pathophysiological mechanisms underlying chronic post-burn itch could improve diagnostics and treatments.


Table S-A.1 -Means and standard deviation (SD) of mean peak (MP) frequency and centre of gravity (CoG) peak frequency methodologies as well as their intraclass correlations (ICC) during eyes closed (EC) and eyes open (EO) resting state measures per group of patients with chronic post-burn itch and healthy controls
(HCs) at the beginning (T1) and the end (T2) of the experiment. Sample sizes of the patients were n = 14 for EC1 and EO2; n = 13 for EO1; n = 15 for EC2. Sample sizes of the HCs were n = 14 for EC1 and EO1; n = 13 for EC2 and EO2. CI = confidence interval. df = degrees of freedom. * p < .05. ** p < .01. *** p < .001 <.001***

Table S-A.2 -Means and standard deviation (SD) of mean peak (MP) frequency measures at the beginning (T1) and end (T2) of the experiment as well as their intraclass correlations (ICC) separately for eyes closed (EC) and eyes open (EO)
resting state and for the patients and healthy controls (HCs). Sample sizes of the patients were n = 14 for EC and n = 12 for EO. Sample sizes of the HCs were n = 13. CI = confidence interval. df = degrees of freedom. * p < .05. ** p < .01. *** p < .001         .

Power
For histamine stimulation when including outliers (Table S-D.2), no significant main or interaction effects of group (patients with chronic post-burn itch/healthy controls) or stimulation side (ipsi-/contralateral) on power were found in any frequency band. However, significant main effects of ROI were found in the theta, alpha, and beta bands (see Table S

Mean Peak Frequency
RM-ANOVAS did not find significant interaction or main effects of group (patients with chronic post-burn itch/healthy controls), ROI, or stimulation side (ipsi-/contralateral) on mean peak in the theta or alpha bands (Table S-D.4).
However, in the beta band there was a significant main effect of ROI on mean beta peak frequency (see TableS-D.5 for post-hoc pairwise comparisons).

Theta Power
During electrical itch stimulation at participants' individual "must-scratch" threshold, an RM-ANOVA (Table S-E.2) suggested a significant main effect of ROI and stimulation side (ipsi-/ contralateral) on theta power, as well as an interaction effect between stimulation side and ROI for theta power (see Table S

Alpha Power
An RM-ANOVA (Table S-E.2) suggested nonsignificant main and interaction effects of group (patients with chronic post-burn itch/healthy controls) but a significant main effect of ROI on alpha power (see Table S-E.4 for post-hoc pairwise comparisons).
When three outliers were removed for a sensitivity analysis, there was still no main effect of group on alpha power (F(1, 21) < .01, p = .926, ηG²< .01).

Beta Power
An RM-ANOVA (Table S-E.2) suggested a significant main effect of ROI (see Table   S-E.4 for post-hoc pairwise comparisons) but no significant main or interaction effects of group (patients with chronic post-burn itch/healthy controls) on beta power.

Table S-E.2 -Comparison of electroencephalography (EEG) power outcomes between patients with chronic post-burn itch (n = 13) and healthy controls (HCs; n = 13) during
electrical itch stimulation at participants' "must-scratch" threshold for separate regions of interest (ROIs). All variables were square-root transformed before performing these analyses. The

Table S-E.3 -Post-hoc pairwise comparisons of interaction effects between stimulation side and regions of interest (ROIs) on electroencephalography (EEG)
theta power during electrical itch stimulation at participants' "must-scratch" threshold. All variables were square-root transformed before performing these analyses. The means and standard errors (SE) are post-hoc estimations based on the variables included in the repeated-measures analysis of variance. Whether the left or right hemisphere were ipsi-or contralateral to the stimulation side differed across participants due to randomisation of stimulation side. The ROI electrodes refer to:

Theta power
During CPT pain stimulation, an RM-ANOVA (Table S-F.2) did not suggest main or interaction effects of group (patients with chronic post-burn itch/healthy controls) on theta power. However, the analysis did suggest a significant main effect of ROI on theta power and an interaction effect between ROI and stimulation side (ipsi-/contralateral) on theta power (see Table S

Alpha power
During CPT pain stimulation, an RM-ANOVA (Table S-

Beta power
During CPT pain stimulation, an RM-ANOVA (Table S-